Salbutamol in 5q spinal muscular atrophy: a systematic review and meta-analysis of efficacy and safety.

Salbutamol, an agonist of the β2-adrenergic receptor, has demonstrated positive outcomes in spinal muscular atrophy (SMA). This systematic review and meta-analysis aimed to investigate its efficacy and safety in patients with SMA. Four biomedical databases (PubMed, Embase, Web of Science, Cochrane Library) and three conference abstract repositories were systematically searched on 1 February 2025 for related clinical studies. Primary outcomes were the motor function, respiratory function, and the peripheral survival motor neuron (SMN) transcript levels of SMA patients pre- and post-salbutamol. Secondary outcomes included musculoskeletal function metrics, patient-reported symptoms, and adverse events. A total of eight studies involving 154 subjects were included in the final analysis. Qualitative analysis revealed that a significant number of patients reported subjective improvements. Additionally, salbutamol has been shown to improve respiratory function and contribute to weight gain in certain younger individuals. Meta-analysis demonstrated that, in two selected studies, patients under 6 years old showed a substantial improvement in the Revised Upper Limb Module (RULM) scores (mean difference (MD) = 3.89, 95% confidence interval (CI) 0.35-7.43, P = 0.03) with no significant heterogeneity. Salbutamol also elevated the levels of peripheral SMN2 full-length transcripts, with statistical significance observed at 6 months (MD = 25.13, 95% CI 16.12-34.13, P < 0.00001) and sustained through to 12 months.

Conclusion:  Salbutamol represents a safe therapeutic option that holds considerable promise in the management of SMA, particularly among clinical responders and younger subgroups. Double-blind, randomized, controlled trials are required to confirm these findings.

What is known: • Clinical trials in neuromuscular junction disorders report motor function gains associated with β2-agonists therapy, attributed to both muscle trophic effects and NMJ synaptic modulation. • Salbutamol, a β2-adrenergic receptor agonist, has been shown to increase full-length SMN2 mRNA and functional SMN protein levels in SMA patient-derived fibroblasts.

What is new: • Salbutamol possesses the potential to improve motor function in patients with SMA and represents a safe therapeutic option that holds considerable promise in the management of SMA. • The potential mechanism of salbutamol in treating SMA patients may involve enhancing SMN2 transcript expression via cAMP regulation and increasing SMN protein levels by inhibiting ubiquitin-mediated SMN degradation through the β2 adrenergic receptor-PKA pathway. • Salbutamol emerges as a cost-effective and viable option for SMA patients in underdeveloped regions who lack access to or cannot afford disease-modifying treatments.